Pseudomonas elastase acts as a virulence factor in burned hosts by Hageman factor-dependent activation of the host kinin cascade

Purified Pseudomonas elastase injected subcutaneously into the skin of an Evans blue dye-injected (intravenously) guinea pig caused dye leakage similar to that observed when histamine or bradykinin was injected in the same animal. The histamine-induced dye leakage was ablated in antihistamine-treated guinea pigs, but elastase- and bradykinin-induced dye leakages were not. Local injections of specific inhibitors of the host Hageman factor-dependent bradykinin-generating pathway given immediately prior to elastase injection reduced dye leakage in a dose-related manner. Elastase-related dye release was enhanced when angiotension-converting enzyme inhibitor, a substance which prevents host enzymes from breaking down bradykinin, was injected prior to elastase injection. We conclude that Pseudomonas elastase generates bradykinin in the infected host via a Hageman factor-dependent pathway.